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Published on: March 16, 2020
MicroRNA-301a knockout attenuates peripheral nerve regeneration by delaying Wallerian degeneration
Lanya Fu1,2, Xiaofang Hu1,2, Jiawei Xu1,2
1Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, National Demonstration Center for Experimental Education, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China.
Abstract:
JOURNAL/nrgr/04.03/01300535-202606000-00073/figure1/v/2026-02-11T151048Z/r/image-tiff Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages. Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration, which is a prerequisite for nerve regeneration, we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis. Herein, we found low expression of microRNA-301a in intact sciatic nerves, with no impact of the microRNA-301a knockout on nerve structure and function. By contrast, we found significant upregulation of microRNA-301a in injured sciatic nerves. We established a sciatic nerve crush model in microRNA-301a knockout mice, which exhibited attenua9ted morphological and functional regeneration following sciatic nerve crush injury. The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model. Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration, which was reversible under transfection with microRNA-301a mimics. Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a. Combined with our previous findings in macrophages, we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.
Insights
MicroRNA-301a is crucial for peripheral nerve repair. Its knockout impairs Schwann cell migration and phagocytosis, hindering nerve regeneration after injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Regenerative Medicine
Background:
- Schwann cells and macrophages clear debris during Wallerian degeneration, essential for nerve regeneration.
- MicroRNA-301a's role in Schwann cell function and nerve repair was previously unknown.
Purpose of the Study:
- To investigate the role of microRNA-301a in Wallerian degeneration and peripheral nerve regeneration.
- To determine if microRNA-301a influences Schwann cell migration and phagocytosis.
Main Methods:
- Utilized microRNA-301a knockout mice in sciatic nerve crush and transection injury models.
- Assessed nerve regeneration, Wallerian degeneration, and Schwann cell migration/phagocytosis in vitro and in vivo.
- Investigated the involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway.
Main Results:
- MicroRNA-301a expression is upregulated in injured sciatic nerves.
- MicroRNA-301a knockout mice showed impaired nerve regeneration and inhibited Wallerian degeneration.
- Knockout of microRNA-301a reduced Schwann cell migration and phagocytosis, which was reversible.
Conclusions:
- MicroRNA-301a is essential for effective peripheral nerve injury response and repair.
- It regulates Schwann cell migration and phagocytosis, impacting Wallerian degeneration and regeneration.
- The Yin Yang 1/C-X-C motif receptor 4 pathway mediates microRNA-301a's function in nerve repair.
